The purpose of this study was to determine the ultrastructural localization of a major schistosome circulating antigen — the circulating anodic antigen (CAA) — in the digestive tract of various life cycle stages of Schistosoma mansoni. The presence of CAA was determined by an indirect gold-labeling procedure using CAA-specific monoclonal antibodies. In cercariae, gold label was found in the cytoplasm and in the surface coat of the gut epithelium. A minimal amount of gold particles was also observed in the esophagus epithelium, but this was limited to the luminal surface coat and located proximally to the gut. In 3½-week-old worms and in adult male and female worms CAA was demonstrable in the Golgi apparatus, in cytoplasmic vesicles, and in the luminal surface coat of the gut epithelium. As determined in the adult worms, CAA-positive lysosome-like bodies were only encountered in the most caudal quarter of the gut. In the gut lumen CAA was associated with host white blood cells and with a thick layer of finely granular, moderately electrondense material covering the gut epithelium. The esophagus of these worms did not show CAA reactivity. These results definitely prove that CAA is a gut-specific antigen produced by various life cycle stages of S. mansoni, from the cercarial stage on.